trends of aqua medicines , drugs and chemicals ( AMDC ) in Bangladesh : the last decade ' s ( 2011-2020 ) story to tell

Aquaculture medicines, drugs, and chemicals or simply AMDC, are critical in protecting aquaculture farmers from disease in farmed animals and economic losses. The AMDC is now a well-established industry in Bangladesh, and each year, new products that benefit farmers are launched. This review examined published research information on AMDC over the last decade (2011-2020) and discovered that 41 research publications from various parts of Bangladesh were published, citing the names of 1484 AMDC products. It was discovered that 19 generic antibiotics are well established and widely used in different regions' aquaculture, including shrimp aquaculture. Although some researchers expressed concern about the use of antibiotics in aquaculture, they believe that with proper withdrawal periods and the application of small doses, farmers may avoid economic losses. However, the pathway of the antibiotic introduction in aquaculture setup in Bangladesh was unknown to the researchers, through this review, we revealed the pathway of antibiotics introduction in aquaculture. Additionally, this review revealed that various AMDC products, including oxygen suppliers, growth promoter supplements, disinfectants, raw chemicals, probiotics, pond preparation and management AMDC, and toxic gas removal AMDC, are readily available in various markets throughout Bangladesh. The observation implied that research on the efficacy of various AMDC products in Bangladesh's agro-ecological zones could be conducted, which would aid researchers in deciphering the true nature of AMDC in sub-tropical climates.


Introduction
Successful and profitable aquaculture solely depends on some management norms, including seed selection, pond preparation, nursing, stocking density selection, feeding, routine checkup, disease management, water quality management, and lucrative final product to the end consumer (Biswas et al., 2018;Faruk et al., 2018;Sharif and Al-Asif, 2015). Some extensive aquaculture setup simply used to overlook the disease of aquaculture organisms, whereas they might face economic loss due to high mortality in disease and infections (Leung and Bates, 2013). Preventing mortality and economic loss, some specialist suggested

Research trends of AMDC in the last decade
The extensive literature search on the AMDC (aqua medicines, drugs and chemicals) research revealed that the first published documents were traced on the last decade in 2011 by Hoq et al. (2011) and Khan et al. (2011) from the Mymensingh region. There was an interval of AMDC research publication found in 2013; but from the following year, the journey continued, and the last publication of the previous decade was traced by the research of Ullah et al. (2020), mainly from the Noakhali district of south-eastern Bangladesh. The trend analysis of AMDC research found a positive and sharp increase at the last of the decade; it is presumed that the new decade (2021-2030) will contribute a large number of research publications on different aspects ( Figure 2).

Area wise research trends of AMDC in the last decade
According to AMDC research, the most documents were published in the Khulna region (34%; 14 documents), followed by Mymensingh (20%; 8 documents), Chattogram (15%; 6 documents), and Rajshahi (12%; 5 documents) ( Figure 3). The Khulna division has a high number of publications due to the presence of universities (Khulna University, Jashore University of Science and Technology, and Khulna Agricultural University), Bangladesh Fisheries Research Institute (BFRI) stations, major shrimp producing regions, and the hatchery industry in this area. Mutual interest between businessmen and research institutions created a bridge for the successful establishment of aquaculture operations in that region (Hasan et al., 2015). However, Mymensingh is located very close to the country's capital city Dhaka, making it the most convenient region for feeding the megacity's millions of residents. Freshwater aquaculture production, particularly Pangas, tilapia, and koi, are very high in this region. The headquarters of BFRI and Bangladesh Agricultural University is also located here, encouraging researchers to conduct AMDC research on various topics in this area. On the other hand, Cumilla is one of the closest districts to the capital city of Dhaka, and the freshwater aquaculture industry is thriving there; numerous animal feed and pharmaceutical companies have established regional offices in Cumilla, and the aquaculture disease consultants are primarily university graduates who share their professional expertise and interests with farmers and businessmen, thereby avoiding some impediments Ullah et al., 2020) (Figure 4). 4.2. Total AMDC reported The literature from 2011 to 2020 reported 1484 names, types, and generics of AMDC from different part of Bangladesh. Among the literature, in 2020, the highest number of AMDC were reported (Das et al., 2020;Hasan et al., 2020;Ullah et al., 2020), followed the year 2017 (208 AMDC), 2014 (196 AMDC), 2019 (189 AMDC) and it is observed some reported AMDC in every year except 2013; due to lack of any published document in 2013, we did not find any AMDC in that year ( Figure 5). The result of this analysis gives an understandable trend that, the farmer's preferences of AMDC is raising in a different part of the country. On the other hand, the reported AMDC from the Chattogram district is comparatively higher (455 AMDC) than in any other part of the country. This is because aquaculture farmers in the Chattogram district have adapted to new technology at a much faster rate (455 AMDC) than in any other part of the country ( Figure 6). In another light, the aquaculture setups in Chattogram, particularly in Cumilla and Noakhali, are extremely intensive in nature, with frequent outbreaks of disease and mismanagement, necessitating the use of AMDC by farmers.

Antibiotics
The uses of antibiotics are not a pleasant phenomenon in aquaculture. The development of antimicrobial drug resistance, hypersensitive reaction, carcinogenicity, mutagenicity, teratogenicity, bone marrow depression, and disturbance of normal intestinal flora are all serious public health implications of antibiotic residues (Miranda et al., 2018;Okocha et al., 2018;Schar et al., 2020). However, uses of antibiotics in aquaculture is regulated by the conventional laws of the state for instance, National drug policy-2005, Fish feed and animal feed act-2010, National livestock development policy-2007, National strategy for ARC (Antimicrobial resistance containment)-2011 and Road map of a national action plan for ARC (Hosain et al., 2021). Nevertheless, several studies of last decades indicated several antibiotics of different generics and trade names were reported from different part of the country. We found alone in 2020, a total of 58 antibiotics were reported from different regions (Figure 7). At the same time, the farmers of Chattogram regions are the major user of antibiotics (56 antibiotics) (Figure 8). The problems of antibiotic uses in aquaculture are recently put into concern by the research of Lulijwa et al. (2020). The research of Lulijwa et al. (2020) provided the data of antibiotic uses in top aquaculture producer countries, including Bangladesh, China, India and Vietnam. However, they reported 19 antibiotics are being used in Bangladeshi aquaculture. The government needs to put this matter into a high priority and concern to impose strict regulation and monitoring at the field level. As Bangladesh is a top aquaculture producer and exporter in the world, if the importer countries will impose a ban on the export of aquaculture products, especially the shrimp and Pangas fillet, it will change our fisheries sector drastically. Another publication from Cumilla  also reported 19 antibiotic generics while many of the antibiotics which are being used by farmers and suggested thru practitioner and consultant practically did not come out in the last decades documents.

Exposure pathway of antibiotics in aquaculture
Uses of antibiotics became burning issue in live food and meat production industries including aquaculture (Lulijwa et al., 2020). In whatever form we use antibiotics in live food production, it used to returns to the end user human and causes considerable complication to the human body, environment and aquatic ecosystems (Brunton et al., 2019;Rasul and Majumdar, 2017). The pathway analysis revealed that, antibiotic vendors with intentional medicinal uses purpose are the major source of antibiotics in aquaculture ( Figure 9). However, the other reason might be uses of cow dung as fertilizer in aquaculture pond. Cow dung is widely used raw materials in the aquaculture setup (Jha et al., 2004). The recent study suggested that, use of antibiotics in cattle farm, and later on these cattle farm waste (waste disposal including cow dung, faecal waste and) served as fertilizer in aquaculture which might be severe source of antibiotic introduction of aquaculture setup Sobur et al., 2019). However, the most terrible scenario was reported by Ashrafun et al. (2019), where they revealed the tetracycline resistant E. coli and Salmonella spp. from different source, as tetracycline is widely used antibiotic in aquaculture industry of Bangladesh. So far indiscriminate uses of antibiotics are leading the aquaculture industry to the antimicrobial resistance bacterial species, which can be considered as dangerous phenomenon in long run. Another mentionable source of antibiotics in aquaculture pond is poultry and duck litter disposal in aquaculture pond for increment of phytoplankton and primary productivity of pond. Interestingly, recent research suggested that, some pathogenic bacteria which are available in all farms environment found antibiotic resistance characters, such as Aeromonas hydrophila in broiler farm , Campylobacter spp. in small scale commercial broiler farms (Alam et al., 2020), Campylobacter spp. in poultry farms and live bird markets (Neogi et al., 2020), Salmonella in small-scale commercial layer flocks (Haque et al., 2021), and Campylobacter species in ducks (Uddin, 2018). This phenomenon suggested that use of poultry litter in aquaculture might grow the antimicrobial resistance capacity for the pathogenic microbes in aquatic environments, which obviously will not be a wise idea for the practitioners and aquaculturists. The use of antibiotics in different fish feed are practiced globally, but this were rarely reported (Agoba et al., 2017), however this might be considered another source of antibiotics introduction in aquaculture pond. The waste of pharmaceuticals industry used to dispose directly in the river environments without any treatment; thus some aquaculture setup adjacent to rivers might be affected and the antibiotics might improve the resistance capacity of pathogens. We found some another causes of antibiotic introduction to the aquaculture ponds such as introduction of antibiotics through migratory birds, homestead waste having antibiotic residue disposal to the aquaculture ponds.

Other chemicals
The published documents over the last decades have provided invaluable information to aquaculturists, practitioners, businessmen, policymakers, think tanks, and a variety of other civil groups involved in the aquaculture industry. Apart from antibiotics, the supplier of supplemental oxygen is critical in preventing economic losses in aquaculture operations (Chowdhury et al., 2015). Companies sell the oxygen in granular and tablet form using different brand names, although the ingredients are similar (Table 2). We found many brand names of oxygen tablets from different companies which were reported in the last decade. Growth promoter, for example, various vitamins, minerals, feed premix, additives, fish oil etc. were reported in the last decade by different research groups; ), Chowdhury et al. (2015, Adhikary et al. (2018) and . In the market, ACIMIX premix (combination of different minerals) and vitamin C are very popular, which helps to boost fish growth in a short period. Disinfectant is one of the most used chemicals in the freshwater and brackish water aquaculture (Hasan et al., 2015;Uddin et al., 2020). Due to improper management of the culture setup, overstocking, introducing diseased fish, and various other factors causing diseases to spread in aquaculture ponds. Farmers are advised to use disinfectant and follow consultant guidance in such circumstances. In most cases, a lower pH in the culture setup is to blame for the disease. Liming at an appropriate dose may help raise the pH and completely eradicate existing pathogenic organisms in the aquaculture setup (Chowdhury et al., 2015). However, the most popular disinfectant in Bangladesh found BKC (Benzal konium chloride) chemical, where the active ingredients are n-Alkyl dimethyl benzyl ammonium chloride 40%, stabilized urea 60% (Chowdhury et al., 2015). The market research suggested that the trade name Timsen by Eon Animal Health found most popular among the farmer and aquaculture disease experts. We noticed other disinfectants, such as Virex (ACI Animal Health), Aquakleen (Square Agrovet division); whereas some old-fashioned chemicals work as a magic disinfectant, for example, bleaching powder reported by . The use of raw chemicals in aquaculture solely depends on lime, mustard oil cake, tea seed cake, Potassium permanganate, formalin, salt, malachite green, Methylene blue, diesel, kerosene etc. (Biswas et al., 2018). These chemicals are vastly available in the poison and seed for agriculture-related vending points, grocery stores and chemical shops. The use of the raw chemical is very vast, and they can be used from the eradication of unwanted organisms from culture setup to pond preparation, feeding setup, along disease treatments in aquaculture. In the last decade, many documents reported about the different raw chemicals, where recent publication of Das et al. (2020) reported the highest (7 chemicals) raw chemicals from aquaculture of Rangpur district in Bangladesh (Table 2). However, the appeal of the use of raw chemicals in aquaculture will retain the same due to its effectiveness and low cost. Probiotics are other wings of AMDC, where it plays a vital role to prevent the disease introduction and outbreak by keeping the water quality in good form. However, the use of probiotics in farmers were not so widespread, but this technology used to adopt by most of the educated peoples who already familiar with this technology. The use of probiotics and other chemicals to prevent disease in aquaculture leads to the creation of biofloc technology theory, which is gaining popularity worldwide (Crab et al., 2012). We found many probiotics are available and reported in the last decade, which can be considered a good sign that farmers are adopting new technology to increase production and reduce an economic loss (Akter et al., 2020;Chowdhury et al., 2015;. Water quality management is one of the vital issues for successful aquaculture practice, while it requires regular monitoring and care (Hamli et al., 2013). This review revealed that many water quality maintaining products, including zeolite (ash of volcanic eruption), were very popular. It is also found that, based on single products (Zeolite), many local companies and importer is doing business nationwide. It is due to the zeolite is well known to the farmer, and it is comfortable to use in their aquaculture pond Chowdhury et al., 2015). The use of Yucca (Yucca schidigera) extracts to remove ammonia from pond bottoms and water is extremely popular among farmers. While some experts have suggested using probiotics to remove toxic gases from culture ponds, there are situations while rapid gas removal is required, in which case extract of Yucca is found to be extraordinary. Chien, 2012, 2009). Interestingly dietary use of this plant extract in aquaculture also found effective somewhere else (Güroy et al., 2014;Tidwell et al., 1992). Numerous gas removal products have been reported in the Bangladeshi market. In contrast, a recent publication indicated that the use of gas removal products (16 in total) are popular among farmers in Bogura (Akter et al., 2020) ( Table 2). Biol.

Conclusions
Aqua medicines, drugs, and chemicals (AMDC) research trends indicated that use of AMDC increases significantly among farmers, while aquaculture is also gaining popularity among new entrepreneurs. Young entrepreneurs are becoming more involved in aquaculture and embracing new technologies. While the product profiles of various AMDC companies provide insight into the products' performance, the researchers are unaware of efficacy results on the following products in various Bangladeshi agro-ecological zones, which can be interpreted as a significant research gap in the area of AMDC products and research. While these AMDC products were imported from various tropical and temperate aquaculture countries, and the results were satisfactory to farmers and consultants, more attentions are required before importing any new AMDC products into Bangladesh in accordance with the country's existing agrochemical laws.